+Open data
-Basic information
Entry | Database: PDB / ID: 8yut | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the amthamine-bound H2R-Gs complex | ||||||
Components |
| ||||||
Keywords | MEMBRANE PROTEIN/IMMUNE SYSTEM / GPCR / H2R / Histamine Receptor / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information gastric acid secretion / Histamine receptors / histamine receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta ...gastric acid secretion / Histamine receptors / histamine receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
Authors | Shen, Q. / Tang, X. / Wen, X. / Cheng, S. / Xiao, P. / Zang, S. / Shen, D. / Jiang, L. / Zheng, Y. / Zhang, H. ...Shen, Q. / Tang, X. / Wen, X. / Cheng, S. / Xiao, P. / Zang, S. / Shen, D. / Jiang, L. / Zheng, Y. / Zhang, H. / Xu, H. / Mao, C. / Zhang, M. / Hu, W. / Sun, J. / Chen, Z. / Zhang, Y. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Adv Sci (Weinh) / Year: 2024 Title: Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs. Authors: Qingya Shen / Xinyan Tang / Xin Wen / Shizhuo Cheng / Peng Xiao / Shao-Kun Zang / Dan-Dan Shen / Lei Jiang / Yanrong Zheng / Huibing Zhang / Haomang Xu / Chunyou Mao / Min Zhang / Weiwei Hu ...Authors: Qingya Shen / Xinyan Tang / Xin Wen / Shizhuo Cheng / Peng Xiao / Shao-Kun Zang / Dan-Dan Shen / Lei Jiang / Yanrong Zheng / Huibing Zhang / Haomang Xu / Chunyou Mao / Min Zhang / Weiwei Hu / Jin-Peng Sun / Yan Zhang / Zhong Chen / Abstract: G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. ...G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors HR and HR couple with G- or G-proteins respectively. Here, three cryo-EM structures of HR-G and HR-G complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in HR, wherein the amino group interacts with E206 of HR instead of the conserved D114 of other aminergic receptors. Furthermore, comparative analysis of the HR-G and HR-G complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the G and G selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary G- and G-coupling selectivity. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8yut.cif.gz | 210 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8yut.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8yut.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8yut_validation.pdf.gz | 515.4 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8yut_full_validation.pdf.gz | 522.3 KB | Display | |
Data in XML | 8yut_validation.xml.gz | 20.9 KB | Display | |
Data in CIF | 8yut_validation.cif.gz | 32.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yu/8yut ftp://data.pdbj.org/pub/pdb/validation_reports/yu/8yut | HTTPS FTP |
-Related structure data
Related structure data | 39582MC 8yuuC 8yuvC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 43883.762 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS / Cell (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) |
---|---|
#2: Protein | Mass: 39141.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Cell (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Cell (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-Antibody / Protein , 2 types, 2 molecules NR
#4: Antibody | Mass: 13885.439 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Spodoptera frugiperda (fall armyworm) |
---|---|
#5: Protein | Mass: 46456.023 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HRH2 / Cell (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P25021 |
-Non-polymers , 2 types, 2 molecules
#6: Chemical | ChemComp-A1D67 / Mass: 157.237 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H11N3S / Feature type: SUBJECT OF INVESTIGATION |
---|---|
#7: Chemical | ChemComp-CLR / |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: amthamine-bound H2R-Gs complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 62 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 368447 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 38.91 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|